Research explores early intervention strategy for preeclampsia

Dr. Yang Xia, left, and Dr. Rodney Kellems are studying preeclampsia.

Eagerly awaiting the arrival of their first child, Alma Soto was preparing for the big day and her husband, Alex, was building a crib. Then about six weeks before the due date, Alma started feeling pain and went to a hospital. There, she was diagnosed with a serious disorder called preeclampsia that affects millions of pregnant women every year.

“I didn’t know how serious my condition was until I was told that they would do everything they could to make sure my baby went home with a mother,” Soto recalled. “My blood pressure shot up, and my legs were swollen. I was told that I was a walking time bomb.”

Within 24 hours of arriving at the hospital, doctors induced labor. Soto gave birth to Arianna, a 5-pound, premature daughter, who would spend the next two months at the hospital and another three months being carefully monitored at home. Thanks to great care, both daughter and mother recovered fully, and now years later, Arianna is in college.

Currently, the only effective treatment for preeclampsia is delivery of the fetus.

Biochemists at the Medical School are working on an early intervention strategy to help women like Soto. Their work is supported by a $1.8 million grant awarded by the National Institutes of Health’s Eunice Kennedy Shriver National Institute of Child Health & Human Development with funding from the American Recovery and Reinvestment Act of 2009.

Armed with approximately 1,000 blood samples donated by pregnant women, scientists in the laboratory of Dr. Yang Xia, the principal investigator and an associate professor of biochemistry and molecular biology, will run tests to determine if a protein linked to the disease shows up before the onset of symptoms.

If successful, Xia’s work could allow doctors to identify and monitor at-risk women. Xia’s team looks to even prevent or treat the disease by blocking the protein’s activity.

“The clinical management of preeclampsia is hampered by the lack of pre-symptomatic screening and effective therapy,” said Dr. Rodney Kellems, a study investigator and chair of the Department of Biochemistry and Molecular Biology. “The underlying cause of preeclampsia remains a mystery, and treatment options continue to be unsatisfactory.”

Preeclampsia is typically characterized by a sudden spike in blood pressure, increased protein in urine, and the swelling of the hands, feet, and face. The condition affects approximately 7 percent of all first pregnancies and accounts for more than 80,000 premature births in the United States each year. If there is a silver lining, it is that the disease often occurs near the end of a pregnancy when delivery can be induced with relative safety.

Xia’s research involves a type of human protein called an autoantibody that Xia and her colleagues have shown can induce preeclampsia-like symptoms in pregnant mice. The investigators also were able to prevent the preeclampsia-like symptoms by blocking the autoantibody.

“The results of our newly funded study will determine if the autoantibody is a useful pre-symptomatic marker. Another goal of the research is to develop drugs that block the autoantibody,” said Xia, who has co-authored 16 papers on the subject.

Current management of preeclampsia includes stabilization of blood pressure and stabilization of the mother and fetus in order to optimize delivery.

“This is textbook translational research,” said Dr. Sean Blackwell, a study investigator and associate professor of obstetrics, gynecology and reproductive sciences. “The work that is being done with this project is particularly innovative, and Drs. Xia and Kellems are world-class scientists.”

Eleni Tsigas, executive director of the Preeclampsia Foundation, said, “The impact of preeclampsia goes far beyond just a complicated pregnancy. It can have devastating physical, emotional, or economic impact for a woman, her unborn baby, and her family, including death or long-term health complications, so more research into its cause, and especially therapeutic interventions, is desperately needed.”

Other Medical School investigators on the project titled “Autoantibodies in Preeclampsia: Pre-symptomatic markers and therapeutic targets” include Dr. Zheng (Jake) Chen, assistant professor of biochemistry and molecular biology; Dr. Dorothy Lewis, professor of internal medicine; and Dr. Susan Ramin, Emma Sue Hightower Professor and Chair of the Department of Obstetrics, Gynecology, and Reproductive Sciences. Chen, Kellems, Lewis, Ramin, and Xia also are on the faculty of the UTHealth Graduate School of Biomedical Sciences.

UT System streamlines IRB process for collaborative projects

Institutional Review Board (IRB) approval has been simplified for The University of Texas Health Science Center at Houston (UTHealth) researchers working with colleagues at other University of Texas System institutions. After months of negotiations, all 15 UT System components have reached an IRB Reciprocity Agreement, which allows any UT System researcher collaborating on a research study with another colleague at another UT System institution to opt for a single review by one IRB.

“This is an outstanding example of UT System’s effort to lower the barriers to research. This is by far the most comprehensive and far-reaching effort to help researchers by streamlining the review and approval process,” said Dr. Peter Davies, provost and executive vice president for research at UTHealth and UT System IRB Taskforce co-chair.

FAQs

My research study is being conducted at UTMB and UTHealth. Which IRB will review the proposal?

In general, the reviewing IRB will be the location that is the prime recipient of the research award, or where the majority of the subject interaction will take place. If a proposal has already been reviewed and approved by an IRB within the UT System, this IRB may be designated as the Reviewing IRB.

Dr. Susan Wootton, assistant professor of pediatrics, is conducting a research study on flu vaccines in pregnant women with collaborators at UTMB. This research study received approval from UTHealth IRB for both sites at UTHealth and at UTMB. “The entire study team greatly appreciated the support from the UTHealth and UTMB IRBs in getting our study approved quickly. By avoiding duplicative efforts, the study was approved at both sites within three months,” Wootton said.

I am planning a new research study with my collaborators at UT Southwestern. How do I request permission to rely on UT Southwestern IRB for this research study?

The electronic IRB application within iRIS has questions that specifically ask if you would like to rely on another UT System IRB. If you choose yes, the IRB office will review your request and send you written permission. You must send this written permission and a form called Addition of Principal Investigator to the UT Southwestern IRB through your collaborator at UT Southwestern.

Dr. Angela Stotts, associate professor of family and community medicine, is conducting a research study to determine whether rigorous exercise as an adjunct to community drug abuse treatment will improve outcomes. This research study is being conducted at UT Southwestern and UTHealth and was approved by the UT Southwestern IRB for both sites. “Our experience with the new reciprocity agreement has been incredibly smooth and has saved us hours of work. The Clinical Trials Resource Center and the Committee for the Protection of Human Subjects (CPHS) office have been very helpful in providing instruction on this new process,” she said.

My research study has already been approved by UTHealth. I would like to open another research site at UTHSC San Antonio. How should I go about this process?

Your collaborator at UTHSC San Antonio should seek a written Permission to Rely from the UTSHC San Antonio IRB office. You must submit the written permission to rely from the IRB and an Addition of PI form completed by your San Antonio collaborator to CPHS via a Change Request. After review, the CPHS office will send you a written approval for addition of the San Antonio site. You must send this approval letter back to your collaborator. Your collaborator must submit this approval letter to the UTHSC San Antonio IRB and receive an Activation Letter from the IRB before initiating the research study at San Antonio.

CPHS Initiatives to Reduce Regulatory Burdens

Dr. Anne Dougherty, professor of cardiology and chair of the CPHS executive committee, said that the new IRB process fits neatly within the new quality improvement initiative for the UTHealth Human Subjects Protection Program (HRPP) she leads.

“The CPHS Executive Committee is currently reviewing the UTHealth human research protections program in order to minimize the regulatory burdens on investigators while enhancing human subject protections,” she said. “It is a significant milestone in our effort to lower unnecessary and unproductive barriers to research. We hope to minimize duplicative, and sometimes conflicting, oversight of trials that does not add value to the process. When we have firm reason to trust that another institution is qualified to provide thoughtful, conscientious protocol review for the subjects in a trial, a cooperative spirit serves all interests.”

Dr. Robert Feldman, chair of the Department of Ophthalmology and Visual Science, said he believes this agreement will be particularly useful for increasing our ability to recruit more quickly by including multiple UT System sites in clinical trials. This, in turn, will allow participation in more multicenter projects.

“The UT System IRB Reciprocity Agreement clearly demonstrates that reducing barriers to productive research will result in an increase in collaborative proposals between UT Institutions. I appreciate UT System’s willingness to think creatively to improve our overall research effort,” he said.

CPHS is open to other options to reduce duplicative review. Recently, the institution signed a reliance agreement with the Federated IRB at the National Institute of Child Health and Human Development (NICHD) that allows reliance on the NICHD IRB for all protocols being conducted under National Children’s Study.

Dr. Sean Blackwell, associate professor of obstetrics, gynecology, and reproductive sciences is the principal investigator for National Children’s Study at UTHealth. “This is a very positive step, and I am hopeful that UT System will continue to advance these types of smart initiatives in order to facilitate our ability to be competitive with multi-center research,” he said. “As an IRB member, I value the role of the IRB process in the protection of research subjects, but it's also essential that we make this process as efficient as possible. Over-regulation of research will not only delay research discoveries but also slow down evidence-based therapies from reaching patients and prolong the use of unproven and/or unsafe treatments.”

If you are conducting a research trial with colleagues in other UT System institutions, contact the ORSC Office at 713.500.7943 to see if your study would be eligible for review under the scope of this agreement.

Bricker named new director of pediatric cardiology

Dr. Timothy Bricker

Dean Giuseppe Colasurdo, chair of the Department of Pediatrics, has announced Dr. Timothy Bricker as the new director of the Division of Pediatric Cardiology, effective March 4. Dr. Syamasundar Rao, who has led the division since 2002, will remain on faculty.

Bricker comes to the Medical School from the University of Kentucky, where he is the chair of the Department of Pediatrics and holds the Jacqueline A. Noonan Children’s Miracle Network Endowed Chair.

“I am happy to welcome Dr. Bricker to our faculty,” Dean Colasurdo said. “He is a leader in the field of pediatric cardiology with a strong national reputation and deep ties to the Houston community.”

Bricker received his medical degree from The Ohio State University College of Medicine and his Master’s in Business Administration from the University of Chicago Booth School of Business. He completed a pediatric residency with Baylor College of Medicine and a fellowship in pediatric cardiology at Texas Children’s Hospital. Prior to his tenure with UK, Bricker served on the Baylor faculty for 21 years and has consistently been named to the America’s Best Doctors and Top Doctor’s lists.

“With the addition of Dr. Bricker, our faculty now includes the authors of the major textbooks on heart disease in children,” Dean Colasurdo said. “The other ones being Dr. Rao and Dr. Arthur Garson.”

“We are looking to Dr. Bricker to enrich and build upon the strong foundation Dr. Rao has created,” said Susie Distefano, CEO of Children’s Memorial Hermann Hospital.

Dean Colasurdo also expressed his gratitude to Rao for his many years of service.

“My greatest appreciations to Dr. Rao, who is a world-renowned interventional cardiologist,” Dean Colasurdo stated. “He attracts patients from around the world with his innovative clinical techniques and academic reputation. He has made tremendous strides in the division, including creating accredited fellowship programs in pediatric and interventional cardiology.”

Applications now being accepted for Hitoshi Nikaidoh Award

CHRISTUS Foundation for HealthCare is seeking applicants for the Hitoshi Nikaidoh Memorial Award. The award is given twice a year to third- or fourth-year medical students, medical residents, or physicians in their first five years of practice to perform medical mission work either domestically or abroad.

Up for debate

Drs. Kenneth Shine, from left, Pauline Rosenau, William Sage, and Leonard Zwelling participate in the seventh annual panel discussion presented by the George Fleming Center for Healthcare Management and co-sponsored by the UTHealth Institute for Health Policy Jan. 27 at the UTHealth School of Public Health. The topic of the discussion was healthcare reform diagnosis and prognosis.— Dwight C. Andrews, Office of Communications, Medical School

Grand Rounds in Clinical Ethics presented by the John P. McGovern Center for Health, Humanities and the Human Spirit: Dr. Shih-Ning Liaw, assistant professor of pediatrics, presents, “A Tale of Two Drownings: The Ethics of Pediatric Palliative Care.”Noon–1 p.m., MSB 1.006.
CME and CNE credits are available to attendees. For more information, visit the website.

February 22

Research Coordinator Forum: Efren Pena and Dr. Robert Nobles, Office of the Provost and EVP Research, present, “Research Billing Compliance.”11:30–1 p.m., MSB 2.135.
Lunch will be available for the first 50 attendees. Registration is not required.

February 23

Dean’s Lecture: Dr. Mortimer Mishkin (The National Institutes of Mental Health) presents, “Speech and Auditory Memory: How Deep Is Their Connection.”4 p.m., MSB 3.001.
A reception will follow the lecture.